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📈 Monday data: The bottleneck isn’t intelligence
In the AI Investment Brief today: CapEx updates and lease commitment breakdowns Anthropic co-founder Jack Clark recently said in a speech at the IMF that the singularity has begun: For many years, researchers and science fiction authors have forecast a future in which AI systems drastically increase the pace of overall scientific and technical progress, making things move so quickly that it is hard for humans to keep up. They call this the singularity. I believe that this year we have gained convincing evidence that it has now begun. This follows Anthropic’s claim that in August, 26% of its AI R&D was led by Claude, with a human supervising its work. In October, OpenAI posted 719 math manuscripts1 made by its internal model. Math and coding are two fields where a research loop can close without leaving the desk. But can the loop close in the rest of science? Subscribe The loop is real The idea is not new. Mathematician Irving John Good, who had worked with Alan Turing at Bletchley Park, argued that a machine smarter than us “could design even better machines; there would then unquestionably be an ‘intelligence explosion,’ and the intelligence of man would be left far behind.” The Gödel machine, a self-improving computer that can rewrite its own code better than its prior, was first proposed in 2003. In 2025, researchers at Sakana AI and the University of British Columbia set out to show that this was possible. Their agents iteratively improved their own code through a feedback loop, resulting in gains of 30 pp on SWE-bench and more than 15 pp on Polyglot, testing coding skills beyond Python. The idea has since been tested in other labs. A Gemini-powered agent called AlphaEvolve found a faster matrix multiplication kernel used for training Gemini, speeding up the kernel by 23% and cutting Gemini’s training time by 1%. In China, MiniMax reported that its M2.7 model worked on improving its own agent’s harness, skills, sampling and memory. Over 100 rounds of rewriting led to a 30% gain, per its internal evaluations. In each case, what was being rewritten was not the model itself but everything around it. Is it better than human work? In September this year, in what seemed like a milestone, an AI-built agent proved as good at improving other AI agents as a human-built one. It did that in what appeared to be half the steps. But the result was inconclusive: the differences between runs were greater than the difference between the AI- and human-built agent results. Nonetheless, this is increasing the chatter around recursive self-improvement (RSI) in AI. Google’s Sundar Pichai said that “you have RSI loops along with AI researchers in various aspects of model development.” Sakana AI published a paper on RSI through multi-agent collaboration, finding that after two cycles its system scored 1.2–1.6x better per output token than the base model across four research benchmarks. Ramez Naam challenges that view. He splits AI self-improvement into five overlapping types. The first four describe how autonomous the AI is; so far, only types 1 and 2 have been observed. The fifth type describes accelerating returns, and he notes that greater autonomy doesn’t guarantee a takeoff scenario. Instead, each round of self-improvement would need to deliver at least as much as the last. The results from Sakana, AlphaEvolve and MiniMax above might look like type 3 or type 4 autonomy. But in each case, the AI wasn’t updating its own weights directly, only the ancillary parts — the harness, the memory. And where Claude leads its own R&D, for now a human still supervises.
Audi Builds in Georgia, and the Politics Come With It
The German luxury brand plans a $4 billion US factory to escape punishing import tariffs, but its CEO’s appearance alongside Donald Trump has turned a strategic manufacturing decision into a governance headache back home.
Youth Mental Health Action Lab: Strengthening School-Based Mental Health
Cross-agency teams from five states convened in Annapolis, Maryland, Oct. 7-8, for NGA’s second Youth Mental Health Action Lab focused on strengthening approaches to addressing the youth mental health crisis in schools.
Joe Burrow Silences Fans Who Called Him ‘Washed’ and ‘Overrated’ as Bengals Shut Down Ravens
Fans have learned not to count out Joe Burrow too quickly. The Cincinnati Bengals quarterback, 29, and his team had what The Athletic described as one of their worst offensive halves in recent history against the Baltimore Ravens on Sunday, October 25. Burrow went 6 of 12 passing for 43 yards in the first two […]
Rhode Island FC and Centreville Bank Stadium Name Lou DePaoli as President of Business Operations
Seasoned sports executive brings over 30 years of leadership experience, deep New England roots to Rhode Island FC and Centreville Bank Stadium PAWTUCKET, R.I. (Oct. 26, 2026) – Today, Rhode […]
Scientists Tested a Toad Venom Psychedelic on Treatment-Resistant Depression. Here's What Happened.
A clinical trial shows promising results, but many questions remain.
Business Monday: Longtime Kona sports bar rebrands under new name, Voyagers
The Kona Canoe Club, once a sports bar owned by famed LA Dodgers pitcher Don Drysdale, launched a new name and menu in September: Voyagers.
Europe takes cancer science into immunology
Inspired by technology and insights gleaned from cancer research, Europe is leading the quest for a new generation of therapies in immunology and inflammation. Immunotherapy has revolutionised cancer therapy and become standard of care in many areas of oncology but it has also begun to change outcomes in inflammatory and autoimmune diseases.
Selecting WHO Director-General: The Job Nobody Has Described (Part II)
The World Health Assembly (WHA) will choose WHO’s ninth Director-General next May without having defined the job. Part I of this analysis sought to learn
NASA, USDA Sign Agreement Advancing Earth Science, Agriculture
NASA and the U.S. Department of Agriculture (USDA) have signed a Memorandum of Understanding expanding cooperation in Earth observation, geospatial analytics,
Three things we learned from the United States Grand Prix
Kimi Antonelli stands at the threshold of Formula One's hall of fame, needing just two more points to become the sport's youngest champion and first Italian for 73 years.With five races remaining, AFP Sport looks at three things we learned from the 20-year-old Italian's ninth win of an outstanding season: Antonelli maturing fast and adding strategic authority to his arsenal A brief comparison with the misfortunes and struggles of his teammate and nearest rival George Russell reveals how rapidl
As Trump brags about U.S. oil and gas company profits, his stocks gained millions during Iran war
A report from congressional Democrats found the president purchased millions in oil and gas stocks during the war.
Food Safety Risk Assessment: How Scientists Evaluate Chemical and Microbial Hazards
Food safety risk assessment combines evidence about chemical toxicity and microbial hazards with dietary exposure estimates to evaluate potential health effects. Scientists account for combined exposures, susceptible populations, and uncertainty to guide monitoring, regulation, and preventive measures.
D. C. Circuit Review: Reviewed – Some unfinished business
The D. C. Circuit published two opinions last week in cases that were argued last term. Mennonite Church USA v. DHS, No. 25-5209, which was heard in February of this year, involved a challenge to the Trump Administration’s policy of pursuing immigration-enforcement operations at houses of worship. Prior to 2025, the federal government largely maintained […]
We May Be Living Through a Sixth Mass Extinction—but Scientists Think Some of the First Five Never Happened
New AI-powered research questions whether a majority of Earth’s mass extinctions were as abrupt as previously believed.
Bailey, Crosby clash over City Hall, carpetbagging and partisan politics in fierce San Diego City Council race
Nicole Crosby, a Democrat, appears to be the favorite over Richard Bailey, a Republican-turned-independent, in District 2, where registered Democrats far outnumber Republicans.
25 faculty recognized for esteemed accolades in research, academia
Rice's winners of highly prestigious and prestigious awards were recognized Oct. 21 to celebrate Rice faculty who have earned these accolades, demarcated by the Organization of the National Research Council and the Association of American Universities.
Rice engineering students become first university group inside Apple’s new Advanced Manufacturing Center
Rice University materials science and nanoengineering students gained hands-on experience in AI server production and surface-mount technology during an exclusive tour of Apple’s new Advanced Manufacturing Center in Houston.
Rezilient Health Appoints Lisa Ness as Chief Revenue Officer
Rezilient Health announced today that Lisa Ness, MBA, RD, CDE, has joined the company as Chief Revenue Officer. Ness brings more than 30 years of healthcare industry experience, including executive leadership roles at QuadMed, CareATC and Proactive MD. In her new role, she will lead Rezilient's commercial growth strategy as the company expands its relationships with self-funded employers, brokers and health systems nationwide.
View from the top: Felix Morgan, Trucordia
Felix Morgan, CEO and chairman of Trucordia, joined the Lindon, Utah-based brokerage, formerly known as PCF, in 2021 as chief financial officer and later became chief operating officer.
Partner1 Renews WBENC Women's Business Enterprise and Women-Owned Small Business Certifications
Recertification caps a year in which founder and CEO Juhi Saha was named to Inc.’s 2026 Female Founders 500 and Partner1 was named an Inc. Power Partner for the second year runningPLEASANTVILLE, N.Y., Oct. 26, 2026 (GLOBE NEWSWIRE) -- Partner1, the advisory firm and software platform behind the partnership strategies of fast-growing B2B software companies, today announced it has renewed its Women’s Business Enterprise (WBE) and Women-Owned Small Business (WOSB) certifications from the Women’s Bu
Mike Vrabel is not concerned about A.J. Brown: ‘Just have to get back into a rhythm’
| WEEI 93.7
Trump intensifies anti-Muslim rhetoric against Abdul El-Sayed at Michigan rally
The US president was condemned for remarks that questioned the senate candidate’s loyalty to the country
The markets are starting to act seriously weird. Blame AI
AI’s shaky balance sheets raise questions about circular financing that investors have long questioned but the industry and many traders have swept under the rug.
Chicago banks post strong profits despite macroeconomic shocks
Loan growth remained strong in the third quarter despite rising interest rates, sticky inflation and geopolitical shocks from the war in Iran.
Citizens Turn Out to Protest Collins Appearance at Fundraiser
ROCKPORT — More than 50 people turned out Sunday evening, Oct. 25 to protest a visit by U.S. Sen. Susan Collins, R-Maine, for a reported fundraiser at the Samoset Resort
Health reports - The Daily Reporter
Hancock County Health Department inspects restaurants and public food establishments four times annually. The following inspections are based on information obtained from Retail Food Inspection reports and are routine inspections, unless otherwise noted. “R” denotes violations repeated from a previous inspection.
I cashed in my retirement to open a bookstore
In Atlanta, a former teacher opened a romance bookstore, fostering a community for romantasy readers despite concerns over market saturation.
"Zero" signs that Kennedy is leaving post-midterms
President Trump is happy with Kennedy, and most of his agenda remains unfinished.
Live Nation Entertainment (LYV) Stock Trades Near Fair Value Following Its 121% Run
Live Nation Entertainment has rewarded long term holders, and the stock now trades around US$173.44, which puts its cash generation in sharp focus. With that kind of share price level, the question is whether the current market value can be backed up by the cash flows the business is expected to produce. Over the past 3 years the stock has returned 120.7%, so a lot of future cash flow strength is already being reflected in the price. The company leans heavily on converting concert promotion...
What Happened to the Neanderthals?
Scientists now know that they shared many of the sophisticated abilities of Homo sapiens. So why are we the only humans left standing?
Apple Will Reportedly Stop Making You Feel Like a Thief When You Return an Unopened iPhone
Opening your unopened box just felt aggressive.
New Orleans-based biotech company lured to SC as first for MUSC lab
The company name was deliberately chosen from West African lore: Obatala, the god who shaped the human body. And the New Orleans biotech firm is determined to see that their human-based research lab m...
Wieden+Kennedy launches entertainment division to make movies and shows—with and without brands
W+K Entertainment will develop original projects, starting with a Bad Bunny film, and help clients break into Hollywood.
Smithsonian scientists launch "Lumina" simulation to model early universe
Researchers introduce "Lumina," a massive cosmological radiation-hydrodynamics simulation designed to model the universe's first two billion years
'Wheel of Fortune' Jim Thornton: FBI Never Contacted Witness in Pedo Chatroom Scandal
The woman who says she saw disgraced 'Wheel of Fortune' announcer Jim Thornton in a pedophile chatroom on a plane has NEVER been contacted by the federal agency that would investigate such matters -- the Federal Bureau of Investigation -- TMZ has learned.
Business News: Audemars Piguet Unveils 'The Watch Keepers' - A Digital Platform Offering Certified Pre-Owned Watches
The Le Brassus watchmaker will facilitate sales and auctions of brand-certified timepieces on a digital platform launching in Switzerland and Europe, with plans for expansion to other markets, including the U.S.
Political earthquake in Serbia: The end of the Vucic Era
This is not simply a change of government. It is the collapse of a political order that has defined Serbia since 2012.
Ted Sarandos Swoops Into Seoul as Netflix Celebrates 10 Years in Korea
The streaming gaint's co-CEO joined stars from ‘Squid Game,’ ‘KPop Demon Hunters’ and other Korean hits for a two-day fan festival, while previewing buzzy upcoming titles like ‘Possible Love,’ ‘Tantar...
What is optogenetics? The Nobel-winning science explained
From light to insight: Exploring optogenetics in brain science
The importance of checking in
Even if you’re not actively involved in the conversation on serious injuries and fatalities, you’re likely aware of the occupational safety community’s heightened focus on preventing these incidents.
Kane primed to pip Yamal, Mbappe to Ballon d'Or glory
England captain Harry Kane is the favourite to win a wide open race to be crowned Ballon d'Or winner at a glitzy London ceremony on Monday, with Lamine Yamal and Kylian Mbappe also in the running to be named the world's best footballer.- 'I deserve it' - Yamal finished second to Paris Saint-Germain's Ousmane Dembele last year and the 19-year-old Barcelona superstar seems destined to be a Ballon d'Or winner one day.
He left his Netflix job in Japan and turned a kindergarten into a cinema
After relocating from Los Angeles, Matthew Kelson and his wife decided to raise their two kids in a small Japanese town outside Tokyo.
Can teaching people more about science increase public trust?
We hear about science outreach efforts in Cincinnati designed to spur interest — and the role moms play in shaping science policy.
Dana White Outlines How Movsar Evloev Gets Another Title Shot
UFC president Dana White outlined how featherweight fighter Movsar Evloev could get another title shot at 145 lbs.Evloev was 20-0 in MMA and 10-0 in the UFC heading into UFC 333, but he suffered a brutal second-round knockout loss against UFC featherweight champion Alexander Volkanovski in a failed bid to become the promotion’s new 145 […] The post Dana White Outlines How Movsar Evloev Gets Another Title Shot appeared first on HEAVY.
Daniel Cormier Says Alexander Volkov Should Get UFC Title Shot
UFC commentator Daniel Cormier says that Alexander Volkov deserves to be next in line to fight for the UFC heavyweight title. Volkov — who turned heads this week with a viral clip of him asking UFC president Dana White what he has to do to get a title shot — defeated Rizvan Kuniev at UFC […] The post Daniel Cormier Says Alexander Volkov Should Get UFC Title Shot appeared first on HEAVY.
Trump rails against Bill Maher in his longest Truth Social post ever
President Donald Trump has just penned his longest Truth Social post ever, according to a CNN analysis and a third-party tracking firm.
Three new members join Endowment for Health’s board of direc...
Zach Palmer, Alex Mason and Julia Williams joined the Endowment for Health board Oct. 1, bringing banking, community development and health care leadership expe...
Three new members join Endowment for Health’s board of direc...
Zach Palmer, Alex Mason and Julia Williams joined the Endowment for Health board Oct. 1, bringing banking, community development and health care leadership expe...
Baltimore Orioles Option Deadline 2026: Every Contract Decision Explained
From injury-plagued veterans to high-stakes mutual clauses, the Birds face a roster shakeup as looming contract deadlines force Mike Elias to weigh expensive risks against essential depth.
TOP 10 PLAYERS: Barcelona 1-2 Real Madrid
A very disciplined and crucial effort in defence from Real Madrid
Nu Holdings (NU) Faces Political And Leadership Questions, Does It Look Fairly Valued?
Election shock and leadership change put Nu Holdings in focus Nu Holdings (NYSE:NU) is under fresh scrutiny after a Brazilian election result sparked a double digit overnight drop in the stock, just as the fintech disclosed a pending chief technology officer departure. Over the past month, Nu Holdings has seen an 11.55% share price return and a 4.12% gain over seven days, even though the year to date share price return is down 10.93% and the one year total shareholder return has declined...
9th Circuit questions DOJ demand to set aside 20,000 California mail ballots
A panel of federal appellate judges on Sunday questioned the timing, constitutionality and authority of the Justice Department's demand
Dominant Doncic scores 52 as Lakers beat Jazz
Luka Doncic scored a monster 52 points as the Los Angeles Lakers maintained their perfect start to life after LeBron James with a 132-123 defeat of the Utah Jazz.From there Doncic and Reaves were relentless, outscoring the entire Jazz offense in the final quarter between them, as the new-look Lakers moved to a perfect 3-0 start.
The best apps for tracking your reading and discovering new books
There are many apps that are designed to help you track your reading and discover new books, so we compiled a list of some of the best ones.
Vandalia Health recognized for digital health achievement
Vandalia Health earned Level 9 recognition in both acute and ambulatory care in the 2026 Digital Health Most Wired Survey.
Politics Unplugged (Full Episode) Oct. 25, 2026
On this week's episode of Politics Unplugged, host Dennis Welch and a panel break down Arizona's election landscape one week out: pessimistic voter mood, suppressed independent turnout, lagging GOP enthusiasm, and Democrats gaining ground. They discuss Elon Musk's late spending in competitive House races and debate the impact of big money flooding the state. The show also covers a widely condemned Ohio attack ad by Vivek Ramaswamy that weaponizes a rival's childhood abuse—drawing praise from Trump and Vance but bipartisan outrage.
He's competed in 21 Hyrox races around the world: 3 top host cities
Lau Wen Loong has been competing in Hyrox races for two years and feels super fit. "I never imagined I could be faster than my younger self."
Local business expert recommends reporting scams via BBB scam tracker
The Better Business Bureau warned the public about phishing scams and advised consumers to regularly check their bank and credit card statements to identify fraudulent activity.
Local business expert recommends reporting scams via BBB scam tracker
The Better Business Bureau warned the public about phishing scams and advised consumers to regularly check their bank and credit card statements to identify fraudulent activity.
Young Scientists Congress: New technologies take centerstage at science exhibition in Wenzhou
The World Young Scientists Congress has opened in Wenzhou, east China's Zhejiang Province. More than 800 scientists and entrepreneurs from over 60 countries and regions are attending the event which includes an exhibition of the latest technologies. We spoke with some of the visitors to the event.
Probi and Symrise spotlight new clinical evidence at SupplySide Global
At SupplySide Global 2026, Symrise and Probi present new clinical findings for skin radiance and digestive health alongside a stable probiotic designed to broaden formulation options for brands
Vucic Concedes Electoral Defeat, Setting Stage For New Era Of Serbian Politics, Relations With West
Aleksandar Vucic, Serbia's former president and dominant political figure for more than a decade, conceded defeat to the student-led protest movement in the country's parliamentary elections, potentially ushering in a new era of politics more closely aligned with Europe and away from the Kremlin.
9th Circuit panel questions basis for feds' request to block 20,000 California ballots
Two judges questioned the Justice Department's lawyer about how the Trump administration's position squared with the law.
Early voting underway in Michigan
Early voting began Saturday, Oct. 24 in Michigan. County officials say the first day of early voting went well and more than half of mail-in ballots have already been returned.
Veteran Makers Market highlights importance of supporting veteran-owned businesses
The Veteran Makers Market spotlights veteran-owned businesses, encouraging shoppers to support those turning military skills into local success.
Over 300 students learn science and technology at CCSD Family STEM Day
Over 300 students learned about science and technology industries at the Clark County School District Magnet Schools Family STEM Day on Saturday.STEM Day as he
After testing all major mobile browsers, this one finally earned my default spot
Looking beyond Chrome paid off with the best browser experience
Oregon State gains ground in AP poll after bye week
The Beavers gained votes in the AP poll, but dropped in the coaches poll.
Volkswagen Bet On Xpeng To Save Its China Business, But Buyers Aren't Showing Up
Volkswagen once dominated China’s automotive market, but the rise of domestic electric vehicle manufacturers has turned its fortunes upside down. Hoping to regain lost ground, the German automaker partnered with Chinese EV specialist Xpeng in ... Read more
🎥 Kylian Mbappé's lucky goal against FC Barcelona
Kylian Mbappé opened the scoring against FC Barcelona this Saturday, October 25.A truly unexpected goal.With both teams looking sluggish from the start, it took until the 42nd minute for the deadlock...
Mobile County Health Department updates sentinel chicken test
It concerned testing for St. Louis encephalitis
Alaska Democratic Senate candidate Mary Peltola and her family suffer minor injuries in car crash
Peltola required medical attention after the accident, which happened when another vehicle crashed into the one transporting Peltola and her family, the campaign said.
Frisco Muslims vote in Texas midterms marked by anti-Islam rhetoric
Texas politicians have campaigned on banning Shariah this cycle. Muslim voters are encouraging their fellow believers to get involved in politics.
Tampa technical institute expands bilingual health care career training
Aguilas International Technical Institute has opened a larger Tampa facility, expanding bilingual career training as health care demand grows locally.
Two Georgia Bulldogs ranked among college football's top-25 players
Two Georgia Bulldogs earned top-15 spots on ESPN's midseason top 25 college football player rankings.
USC Drops Out of AP Top 25 Poll After Wisconsin Loss, UCLA Rises Again
Both the USC Trojans and the UCLA Bruins had their rankings in the Associated Press Top 25 poll following their results from Saturday. View this post on Instagram A post shared by LA Sports Report (@lasportsreport) What Happened to USC’s Ranking? Following their loss to Wisconsin on Saturday, USC dropped out of the Top 25. […] The post USC Drops Out of AP Top 25 Poll After Wisconsin Loss, UCLA Rises Again appeared first on LA Sports Report.
Elizabeth Holmes film puts up a fight against 'Clayface' at box office
A movie set in the world of Batman and a three-hour documentary about Elizabeth Holmes went head-to-head at the box office this weekend, and it turned out to be a closer contest than expected.
Elizabeth Holmes film puts up a fight against 'Clayface' at box office
A movie set in the world of Batman and a three-hour documentary about Elizabeth Holmes went head-to-head at the box office this weekend, and it turned out to be a closer contest than expected.
Nigeria widens hunt for possible Ebola cases
Nigeria has widened a hunt for potential Ebola cases, with an additional nine contacts traced, health authorities said Sunday.The initial 44 contacts were health care workers, while the additional nin...
Made in Tarrant: Family turns sports card hobby into baseball stadium business
Rebecca Gallagher and her family opened their business in Choctaw Stadium in Arlington a few weeks ago. They hope it can grow into a place for community.
Made in Tarrant: Family turns sports card hobby into baseball stadium business
Rebecca Gallagher and her family opened their business in Choctaw Stadium in Arlington a few weeks ago. They hope it can grow into a place for community.
Union County Best of the Best Business of the Year Magnolia Renovations Joshua Andrews, owner
What was your reaction when you learned your business had been named Business of the Year?
'You Can See Everything' surges with $19.5M at box office; 'Clayface' takes No. 1
DC Studios scored a modest, R-rated win with “Clayface,” landing a $24 million opening weekend, according to studio estimates Sunday. But the biggest success story in theaters remained A24’s...
'You Can See Everything' Surges With $19.5M at Box Office; 'Clayface' Takes No. 1
NEW YORK (AP) — DC Studios scored a modest, R-rated win with “Clayface,” landing a $24 million opening weekend, according to studio estimates Sunday. But the biggest success story in theaters remained A24’s Elizabeth Holmes documentary “You Can See Everything,” which pulled in $19.5 million in its ...
China Star Entertainment (SEHK:326) Stock Looks Richly Priced As Its 8.6x Run Continues
China Star Entertainment has logged very strong multi year share gains, so the key issue now is whether the current price can be supported by the value of assets on its balance sheet. For anyone looking at the stock today, the immediate question is how that share price lines up against its book value. Over the past 3 years the stock has returned about 8.6x. This puts a lot of weight on whether the underlying equity in the business justifies this kind of move when you compare it with the...
Clayface Takes First Place While Holmes Documentary Grows in Week Two
Clayface opened with $24.5M, while A24's three-hour Elizabeth Holmes documentary You Can See Everything grew 25% in its second weekend.
Bloomington business continues to blossom
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In West Maui, Democrat-turned-Republican defends House seat against Lahaina Strong organizer, local business advocate
Incumbent Rep. Elle Cochran, Green Party candidate Pā’ele Kiakona and Democratic nominee Sne Patel are battling to represent West Maui at a pivotal time in the fire recovery.
Americans have a grief problem we still call a mental health problem
OPINION — Americans have become much better at talking about mental health. We have learned words such as trauma, post-traumatic stress disorder, depression, anxiety, burnout, compassion fatigue and moral injury. That vocabulary matters.
Blue Ivy takes the stage, Destiny’s Child reunites at Jay-Z’s L.A. concert
Blue Ivy Carter joined dad Jay-Z onstage for a piano accompaniment, while mom Beyoncé cheered her on with two very special guests.
In Texas Senate Race, Talarico Leans Into Growing Rivalry With Elon Musk
On the trail, James Talarico, the Democratic Senate nominee, has increasingly gone after Mr. Musk, a critic of his who has given big to a group aligned with the Republican candidate, Ken Paxton.
ESMO: Roche touts ‘convincing’ phase 3 KRAS data after win over rivals
Roche has shed more light on its investigational KRAS G12C inhibitor's phase 3 victory over Amgen’s Lumakras and Bristol Myers Squibb’s Krazati. The open-label Krascendo 1 trial enrolled 338 people with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC). Patients who had already received a KRAS G12C inhibitor or pan-KRAS/RAS inhibitor were excluded from the trial. Participants received either divarasib once daily, Lumakras once daily or Krazati twice daily. Roche announced back in July that divarasib had demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS), meeting the trial’s primary and key secondary endpoints. But the Swiss pharma had been holding back the detailed data until now. At the European Society for Medical Oncology (ESMO) Congress in Madrid, Roche revealed that median OS for the 167 patients who received divarasib was 17.7 months, compared to 12 months for the 171 patients who received Lumakras or Krazati. The benefit was similarly clear when it came to median PFS, which stood at 9.8 months versus 5.7 months, respectively. A total of 44% of patients receiving divarasib were alive without disease progression at one year, compared to 24% of the control group, according to Roche’s presentation. It was a similar story for the objective response rate, which came in at 58% for divarasib versus 32% for the control group, while median duration of response was 11.9 months versus 6.9 months. Stefan Frings, M.D., Ph.D., deputy chief medical officer at Roche Pharma, told Fierce that the data made for a “very comprehensive, strong package, which should be convincing to health authorities.” “It’s an important advance for patients with lung cancer,” Frings said in an interview at a Madrid hotel during the conference. “It's a second-line setting, and patients who receive divarasib benefit compared to the current first-generation KRAS G12C inhibitors by having far longer overall survival,” he continued. “They live longer. They have better progression-free survival, better response rates, and with a safety profile which is—if [anything]—even better,” he said. According to Roche, 4.8% of patients receiving divarasib discontinued treatment due to treatment-related adverse events, compared to 11.7% in the control group. Serious treatment-related adverse events were also less common with divarasib, at 7.8% versus 15.2%. Roche’s confidence in divarasib had been building even before this phase 3 success. The candidate had already shown better potency and selectivity than the incumbent KRAS G12C inhibitors Krazati and Lumakras in preclinical tests. After cross-trial comparisons suggested that the edge translated into better clinical outcomes, Roche axed a study comparing divarasib to the chemotherapy docetaxel and went toe-to-toe with Lumakras and Krazati. “We designed the drug on purpose with higher potency and better selectivity,” Frings explained. “So, based on preclinical models, we clearly knew it would be superior to the first generation.” “It’s honestly not so frequent that pharma companies go head-to-head,” he added. “But if you want to make a point, if you want to convince payers, prescribers and patients … then a head-to-head win is rather rewarding.” While Amgen and BMS reached the regulatory finish line first for KRAS G12C-mutated, locally advanced or metastatic NSCLC in 2021 and 2022, respectively, they have struggled to capitalize on their head start. Krazati brought in $55 million for BMS in the second quarter, while Lumakras delivered $111 million to Amgen. For its part, Roche is aiming for peak divarasib sales of 1 billion to 2 billion Swiss francs ($1.2 billion to $2.5 billion), according to Frings. The Big Pharma is currently recruiting patients into a phase 3 trial comparing divarasib plus Keytruda against Keytruda plus chemotherapy in previously untreated advanced or metastatic nonsquamous KRAS G12C-mutated NSCLC. Roche has previously suggested that sales in metastatic disease would account for most of the forecast. Frings was tight-lipped on the exact timeline for a regulatory filing but said the Swiss pharma is “certainly keen to get this to as many patients as possible around the world.” Roche has more RAS drugs coming up behind divarasib. The pharma has already launched phase 1 trials of a pan-RAS inhibitor called RG6505 and a KRAS G12D inhibitor dubbed RG6620 in solid tumors. Roche’s partner Chugai Pharmaceutical is also testing a pan-KRAS inhibitor called AUBE00. Roche has made a “deliberate effort” to test a range of RAS drugs, Frings said. “If you have many rare mutations and you are scrambling to find sufficient patients, a pan-RAS inhibitor makes a lot of sense,” he explained.
Who can buy California's voter rolls and why?
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NC business co-owner kills man ‘acting irrationally’ outside Zumba class, police say
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Can social media bans protect young people’s mental health? Early research suggests that bans aren’t the answer
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